Major Depressive DisorderEarly Phase 1NCT03609190
A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine
A Early Phase 1 study testing Ketamine in people with Major Depressive Disorder, run by Psychiatric University Hospital, Zurich.
Trial summary
The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical… Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Jan 2015to Dec 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- treatment resistant depressive episode
- no restrictions regarding antidepressant medication
Who cannot join
- lifetime antidepressant treatment with ketamine
- lifetime recreational use of ketamine
- cardiovascular diseases such as hypertonia, cardiac insufficiency or myocardial infarct in the past six months
- insufficiently treated anemia
- hyper- or hypothyroidism
- lifetime increased intracranial pressure or glaucoma
Show all 16Show fewer
- chronic physical diseases
- hepatorenal dysfunction
- any relevant psychiatric or neurological comorbidity, in particular dementia, epileptic seizures (lifetime), schizophrenia (lifetime), psychosis (lifetime), or post-traumatic stress disorder (current).
- acute suicidality
- substance abuse disorders
- recent heart or head surgery
- metallic body implants
- agoraphobia
- pregnancy
- left handedness
About this study
Official title: Brain Activation Patterns Under Emotional and Neurochemic Stimulation With Ketamine: A Multimodal Neuroimaging Study
The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical applications.
There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action.
The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and depressed patients, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.
- Conditions
- Major Depressive Disorder
- Being tested
- Ketamine, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
i.v. infusion of 0.25 mg/kg S-ketamine over 40 min
PlaceboDrug
i.v. infusion of NaCl over 40 min
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | i.v. infusion of 0.25 mg/kg S-ketamine over 40 min Receives: Drug: Ketamine |
| Placebo | Placebo comparator | i.v. infusion of NaCl over 40 min Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in functional reactivity to emotional stimuli
fMRI BOLD
Measured: Change from baseline to 24h-post infusion
Change in glutamate concentrations in prefrontal cortex
1H-MRS
Measured: Change from baseline to 24h-post infusion
Change in resting-state functional connectivity
rsfMRI
Measured: Change from baseline to 24h-post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2018
- Study startJan 2015
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Psychiatric University Hospital, Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Milan Scheidegger, Psychiatric University Hospital, Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03609190
- Sponsor's protocol ID
- E-31/2008
- Status last verified
- Mar 2019
- First submitted
- 13 Jul 2018
- Last updated
- 20 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Herrera-Melendez A, Stippl A, Aust S, Scheidegger M, Seifritz E, Heuser-Collier I, Otte C, Bajbouj M, Grimm S, Gartner M. Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. Eur Neuropsychopharmacol. 2021 Feb;43:63-70. doi: 10.1016/j.euroneuro.2020.11.017. Epub 2020 Dec 11.
PubMed 33309459Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.
PubMed 30819549
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Activation Patterns Under Emotional and Neurochemic Stimulation With Ketamine: A Multimodal Neuroimaging Study
- ClinicalTrials.gov ID
- NCT03609190
- Acronym / sponsor ID
- E-31/2008
- Conditions
- Major Depressive Disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Psychiatric University Hospital, ZurichUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 1 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical applications.
There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action.
The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and depressed patients, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketaminei.v. infusion of 0.25 mg/kg S-ketamine over 40 min |
| Placebo | Placebo comparator | Drug: Placeboi.v. infusion of NaCl over 40 min |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- treatment resistant depressive episode
- no restrictions regarding antidepressant medication
Key exclusion criteria (16 listed)
- lifetime antidepressant treatment with ketamine
- lifetime recreational use of ketamine
- cardiovascular diseases such as hypertonia, cardiac insufficiency or myocardial infarct in the past six months
- insufficiently treated anemia
- hyper- or hypothyroidism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketaminei.v. infusion of 0.25 mg/kg S-ketamine over 40 min | Drug | Ketamine |
| Placeboi.v. infusion of NaCl over 40 min | Drug | Placebo |
Primary outcome
Change in functional reactivity to emotional stimuli
Time frame: Change from baseline to 24h-post infusion
fMRI BOLD
Change in glutamate concentrations in prefrontal cortex
Time frame: Change from baseline to 24h-post infusion
1H-MRS
Change in resting-state functional connectivity
Time frame: Change from baseline to 24h-post infusion
rsfMRI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
- Derived from this study: PubMed 33309459Herrera-Melendez A, Stippl A, Aust S, Scheidegger M, Seifritz E, Heuser-Collier I, Otte C, Bajbouj M, Grimm S, Gartner M. Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. Eur Neuropsychopharmacol. 2021 Feb;43:63-70. doi: 10.1016/j.euroneuro.2020.11.017. Epub 2020 Dec 11.
- Derived from this study: PubMed 30819549Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ketamine in people with Major Depressive Disorder, run by Psychiatric University Hospital, Zurich.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in functional reactivity to emotional stimuli (time frame: Change from baseline to 24h-post infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03609190, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2019; AzTrials last refreshed its copy on 30 Oct 2026.